The tumor microenvironment has been studied for involvement in cancer growth.
International Patent Application Publication No. WO 2004/009112 describes a pharmaceutical composition and method for use in inhibiting growth of cancer cells in a mammalian subject. The composition includes a urease enzyme, and associated therewith, a chemical entity effective to enhance the delivery of the enzyme to cancer cells, when the composition is administered to the subject. Also disclosed are a method of enhancing the effectiveness of weakly basic anti-tumor compounds, a method assessing the presence, size or condition a solid tumor in a subject, and a gene therapy composition for treating a cancer in a subject. Canadian Patent Application No. 2,493,282 describes similar compositions and methods. International Patent Application Publication No. WO 2014/165985 describes antibody-urease conjugates having therapeutic and diagnostic utility. International Patent Application Publication No. WO 2016/116907 describes pharmaceutical compositions comprising antibody-urease conjugates that are substantially free of unconjugated urease. None of these aforementioned applications describe the treatment of T cells or suggest any effects on the immune system of a subject receiving treatment.
International Patent Application Publication No. WO 2016/090219 describes inhibition of bromodomain proteins in antigen presenting cells to display lower expression of the immunosuppressive molecule PD-L1 for restoring the responsiveness of tolerant T-cells.
Pilon-Thomas et al. (Cancer Res, 2016, 76:1381-1390) describe that neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD-1, or adoptive T-cell transfer improved anti-tumor responses in multiple models.
There is a need for alternative therapies to overcome or mitigate at least some of the deficiencies of the prior art and/or to provide the public with a useful choice for therapies.